Marine mammals are exposed to the oxidative stress induced by hypoxia/reoxygenation cycles yet resist cellular damage. The availability of high-quality genomes promises to provide insights on how this is achieved. In this study, we considered the ubiquitinconjugating enzymes (E2) gene family, UBE2 genes, which encodes enzymes with critical roles in cellular physiology, including the oxidative stress response. The sperm whale was the first marine mammal with a chromosome-level genome, allowing the study of gene family repertories, phylogenetic relationships, chromosome gene organization, and other evolutionary patterns on a genomewide basis. Here, 39 UBE2 genes (similar to human, including 32 intact genes, one partial gene, six pseudogenes) were identified in sperm whale genome. These genes were found on 17 chromosomes and were assigned into 23 subfamilies, 16 subgroups, and four classes based on structural characteristics and functions, phylogeny and conserved domains, respectively. Although the gene structure and motif distribution of sperm whale UBE2 genes are conserved in each subfamily, motif variation and intron gain/loss may contribute to functional divergence. Segmental duplications were detected in six gene pairs, which could drive UBE2 gene innovation in the sperm whale. Contrasting seven cetaceans and five terrestrial taxa, we found that cetaceans have experienced shifts in selective constraint on UBE2 genes, which may contribute to oxidative stress tolerance during the adaptation to aquatic life. Our results provide the first comprehensive survey of cetacean UBE2 genes.